SILVA, K. K. F.; http://lattes.cnpq.br/2728260854265380; SILVA, Kelvyn Kennedy de Figueiredo.
Resumen:
Cancer is considered one of the most common causes of mortality in the world and designates
a set of diseases characterized by the presence of cells in uncontrolled growth, capable of
dividing rapidly and migrating, causing metastasis. Among the therapeutic approaches used in
its treatment, chemotherapy is the method of greatest accessibility and clinical use. However,
adverse side effects and multidrug resistance remain a huge challenge with chemotherapeutic
agents. A promising strategy to address this issue has been related to the prospecting of new
pharmacological agents with specificity for cancer cells. Thus, a favorable branch towards
which new therapies have been turned to concerns compounds with dual effect, i.e., that present
the ability to compromise tumor angiogenesis and induce cancer cell death in a specific and
selective way. Such characteristics can be found in metal complexes, especially those
structurally related to Schiff's bases. Thus, the present study aimed to investigate the toxicity
and the potential anticancer and antiangiogenic effect of four palladium metal complexes
structurally related to Schiff's bases. To this end, experimental protocols for toxicity in cancer
and non-cancer models were performed, in addition to a protocol for investigating angiogenesis.
Initially, to determine the safety in the use of the molecules, the acute toxicity bioassay with
Artemia salina larvae and the hemolytic test in human erythrocytes were performed. Treatment
with the structural precursor pd1 induced a high percentage of hemolysis (103.1 ± 10.2%) and
provided toxicity to the microcrustaceans with CL50 of 58.1 ± 1.1 μM. However, the pd2-5
complexes did not induce damage to the erythrocyte membrane (CI50 >200 μM), as well as
were not toxic to microcrustaceans (CL50 >200 μM) at the tested concentrations, and were
selected for elucidation of their respective biological properties. Subsequently, cell viability
(MTT) assessment assay was performed on human breast cancer tumor cell lines isolated from
triple negative metastatic tumor (MDA-MB-231) and glioma (U-373MG). The four distinct
pd2-5 complexes demonstrated cytotoxic effect, most prominently pd5 with CI50 of 162.5 ±
1.2 μM and 56.6 ± 1.1 μM, respectively, for MDA-MB-231 and U-373MG lineage.
Additionally, the antiangiogenic properties of the molecules were investigated using the
chicken embryonated egg chorioallantoic membrane (HET-CAM) assay. All pd2-5 metal
complexes promoted reduction of the evaluated vascular parameters, including diameter, length
and number of branching of blood vessels. In conclusion, the results obtained so far demonstrate
that all pd2-5 metal complexes evaluated showed anticancer activity and were able to impair
the formation of new blood vessels, with such effects observed in sub-toxic concentrations,
making them, therefore, promising for the prospection of new drugs to strengthen an alternative
line for the treatment of cancer, mainly because they act in two distinct therapeutic targets of
the tumor microenvironment.